Small study shows heart function affected, too

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Beta amyloid deposits were found accumulated in the cardiac tissue of individuals with Alzheimer's disease, who also exhibited compromised myocardial function.

Note that the findings suggest a novel biological framework in which Alzheimer's disease may be viewed either as a systemic disease or as a metastatic disorder leading to heart, and possibly multi-organ failure.

Beta amyloid deposits were found accumulated in the cardiac tissue of individuals with Alzheimer's disease, who also exhibited compromised myocardial function, a small study showed.

By immunoblotting, Federica del Monte, MD, PhD, of Beth Israel Deaconess Medical Center in Boston, and colleagues detected the presence of both amyloid beta-40 and amyloid beta-42 peptides within cardiomyocytes and the cardiac interstitium of the four Alzheimer's disease patients tested.

Alzheimer's disease patients had worse diastolic function at an earlier age as well, according to linear regression analysis, "conforming with the pathogenesis of Alzheimer's disease as a disease of anticipated aging," the authors argued.

"The findings depict a novel biological framework in which Alzheimer's disease may be viewed either as a systemic disease, or as a metastatic disorder leading to heart, and possibly multi-organ failure," del Monte and colleagues concluded. "Alzheimer's disease and heart failure are both debilitating and life-threatening conditions, affecting enormous patient populations. Our findings underline a previously dismissed problem of a magnitude that will require new diagnostic approaches and treatments for brain and heart disease, and their combination."

"Here, we provide novel evidence that the heart and brain can be affected within the same clinical picture. We found that diastolic dysfunction is an early defect in patients affected by Alzheimer's disease, and that intramyocardial deposits of amyloid beta are present in the myocardium of these patients. Because amyloid beta pre-amyloid oligomers affect cell function in the heart as in the brain, it is possible that they may contribute to the observed myocardial dysfunction," the investigators suggested.

"Although these findings will require confirmation in larger populations, they represent an intriguing, and potentially paradigm-shifting advance in our understanding of a highly morbid and largely untreatable disorder," Brian C. Jensen, MD, and Monte S. Willis, MD, PhD, MBA, both of the University of North Carolina at Chapel Hill, wrote in an accompanying editorial.

In this context, Jensen and Willis suggested that several therapies might be candidates for helping the heart and the brain.

"Now that [the authors] have identified amyloid beta in the hearts of patients with Alzheimer's disease, it would be interesting to know how aducanumab affects its abundance and, more importantly, the diastolic function of Alzheimer's disease hearts," according to the duo. Aducanumab -- a novel human monoclonal antibody selectively targeting aggregated amyloid beta -- is under investigation for cognitive benefits in an ongoing phase III trial.

Other potential strategies cited by the editorialists included p38 activation, and transthyretin stabilization.

"Collectively, these therapeutic advances represent rapid success in translating our evolving understanding of the pathophysiological importance of proteotoxicity to improving the lives of patients with potentially devastating neurological and cardiac disorders," Jensen and Willis wrote.

Cardiomyocytes from one patient with Alzheimer's disease showed slower velocities of relaxation and prolonged Ca2+ transients compared with controls, indicating a defect in Ca2+ homeostasis, according to the authors.

"No statistical calculations were performed because we only measured three cardiomyocytes from one Alzheimer's disease case," they acknowledged. However, "although we cannot infer a role for circulating amyloid beta versus a primary defect in Alzheimer's disease cardiomyocytes, it is possible that cardiomyocytes and extracellular infiltrates may combine to determine the overall functional defect in Alzheimer's disease hearts."

Chief among the limitations of the investigation: heart and brain specimen collection was only conducted on patients who were maintained on respiratory support in order to avoid post-mortem depositing of amyloid beta -- thus limiting the histopathological analysis to just four Alzheimer's patients. The retrospective nature of the study also limited its findings to correlations.

"Future prospective research studies directed to assess diastolic function will be required. Those may include cardiac MRI," del Monte and colleagues suggested.

The study was supported by the NIH, American Heart Association, and the Italian Society of Cardiology.

Del Monte and Jensen reported no relevant conflicts of interest.

Co-authors disclosed relationships with DynaMed and Servier.

Willis declared support from the NIH and the Leducq Foundation Trans-Atlantic Networks of Excellence.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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